Beyond bacteria: analysis of the micro-eukorayotic complement of the human gut microbiota

The human body harbours a diverse microbial community belonging to the three domains of life: Bacteria, Archaea and Eukarya. Yet, most of the studies of the intestinal microbiota neglect the eukaryotes, which taxonomic and functional characterisation remains insufficient.Intestinal eukaryotes include protist, fungi and helminths, some of which have purported associations to disease. However, the disease-association of some eukaryotes has been challenged due to its inconsistency across studies. Considering that functional differences have been established even at the intra-genus level, it is possible that some of the observed inconsistencies might trace back to this, mostly uncontrolled, diversity.Eukaryotes appear to be a common component of the intestinal ecology, especially in non-industrialised societies. While some species, like Blastocystis, are common across the world, the largest diversity of gut Eukaryotes is observed in rural communities. Moreover, early evidence demonstrates that eukaryotes might be associated with particular bacterial and archaeal profiles, emphasizing the ecological impact of these microorganisms.Although the biological role of gut eukaryotes is unclear, their assumed pathogenic potential makes them a target for medical interventions. Eradication of alleged parasitic eukaryotes is standard of care, with unforeseen potential consequences to the gut homeostasis.Continuous transition of human subsistence modes is associated with changes in the gut microbiota. Microbial diversity is reduced with industrialisation raising questions about which are the microorganisms we are losing and, with them, what functions are disappearing or evolving within the human gut. The core microbiota represents a group of microorganisms assumed to have co-evolved with the human species and its establishment in the human gut is considered to be a consequence of potentially symbiotic relationships. Multiple studies have described consistent elements of the gut microbiota; however, to date no study has identified a multi-domain core microbiota.This doctoral project contributes to the understanding of the human gut microbiota by concentrating on two gaps: 1) the contribution of the eukaryotic component, and 2) the identification of the multi-domain core microbiome resistant to anthropogenic ecological changes. To address the first gap I have modified LotuS, a bioinformatics tool I co-developed during my PhD (Chapter 2), originally designed to process amplicon-based data for archaeal and bacterial profiling only, and modified to extract and analyse 18S rRNA eukaryotic data. The application of this adaptation is presented in Chapter 3, where I discuss the multi-domain analysis of the gut microbiota of patients with spondyloarthritis.The possible association between Blastocystis and specific microbial profiles is tested in Chapter 4. I studied the prevalence of specific Blastocystis subtypes in the first large scale cohort for gut microbiota research, the Flemish Gut Flora Project (FGFP) and found that the Blastocystis subtype carrier status appears to explain the largest fraction of the variation observed in the gut microbial profile.Finally, I studied the multi-domain microbial profile of Peruvian populations in a continuum of urbanisation. I identified a multi-domain core microbiota shared across four populations, from remote rural to industrialised cosmopolitan, suggesting conserved elements that might be functionally important for the host. In addition, the analysis of covariates showed that the location of the participant (representative of a specific biocultural environment) is the variable that explains most of the observed gut multi-domain microbiota variation.In conclusion, this project emphasizes the need of a comprehensive strategy to better understand the human intestinal ecology. Embracing both, a multi-domain approach as well as an inclusive representation of human diversity will ensure that the conclusions at which we arrive can be generalized.

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